Luca Fusaro: "Crystallization of complex phases in confined space

The aim of this FNRS-funded research project (PDR) is to deepen knowledge of the complex crystalline phases of simple salts. The project aims to strengthen international research activities, which began in 2016 and led to the publication of the first results in Nature in 2021. Read the article online...

In this study, the researchers had isolated four different crystalline phases from a salt of Fampridine, an organic compound used to treat the symptoms of multiple sclerosis. Two crystalline phases showed remarkable complexity, belonging to the special class of Frank and Kasper (FK) phases.

Des cristaux de la Fampridine hydrochlorate ayant une phase complexe de type FK.
Fampridine hydrochlorate crystals with an FK complex phase.

FK phases have been known since 1959 as a large family of metal alloys, but the study demonstrated that simple pharmaceutical molecules can crystallize with similar complexity, something not previously known.

With this new project, the researchers aim to go one step further, using mainly solid-state nuclear magnetic resonance (NMR) and X-ray diffraction (XRD) techniques on powders and single crystals. This study will be carried out in collaboration with other researchers at the NISM Institute (Nikolay Tumanov, Carmela Aprile and Johan Wouters), as well as collaborators working in other countries, such as Riccardo Montis (University of Urbino, Italy) and Simon Coles (Director of the National Crystallography Service (NCS), University of Southampton, UK).

Stéphane Vincent (with UCLouvain): "NPN cofactor synthesis and roles".

The research project (PDR) "NPN cofactor synthesis and roles" is at the interface between fundamental biochemistry and enzymology. It is based on the recent discovery, by a team at UCLouvain, of a new cofactor, named NPN, with a highly original structure. It is a dinucleotide bearing a nickel complex. It is involved in important enzymatic reactions, but little is known about its reactivity, biosynthesis and mechanism of action. Moreover, it is present in 20% of bacterial genomes and 50% of Archaea (archaeobacteria) genomes, but only a tiny fraction of the enzymes employing it have been characterized.

The research project is based on the complementary expertise of Benoit Desguin (UCLouvain, biochemistry) and Stéphane Vincent (bio-organic chemistry). The main aim of the project is to understand the role and mechanism of this cofactor through biochemical, structural and kinetic studies. Analogues of the NPN cofactor will be synthesized by the UNamur team: they will be designed to elucidate the mode of interaction and reaction of the NPN cofactor with the enzymes employing it.

Johan Wouters (with UCLouvain): "Crystallization-based deracémisation in the era of green chemistry".

This research project (PDR) is a co-promotion of Professors Tom Leyssens (UCLouvain) and Johan Wouters (UNamur). It aims to bring the process of uprooting by crystallization into the era of "green chemistry".

Uprooting is a term used in chemistry to describe the process of separating a racemic mixture into its two enantiomers, i.e. the chiral (left and right) forms of a molecule. In the pharmaceutical industry, 50% of marketed drug compounds contain a chiral center, which is essential to their functioning. When one enantiomer has the desired pharmacological effect, the other may be inactive or have undesirable effects. For this reason, new drugs are often marketed as enantiopure compounds (i.e. free of their impure "chiral twin").

The most common way of obtaining chiral drugs still involves the formation of a racemic mixture. This can then be produced by chemical or physical separation techniques, with a yield loss of 50%. If the compound in question is "racemizable", the unwanted enantiomer can technically be converted back into a racemic mixture, resulting in a theoretical yield of 100%. Over the past decade, various crystallization-based uprooting methodologies have been developed. However, all these methods require the use of large quantities of solvent, as they are crystallization processes.

This research aims to take these processes to the next level, not only by making them more efficient (less time-consuming), but also by bringing them into the realm of "green chemistry". To this end, the researchers are proposing mechanochemical variants for conglomerates and racemic compounds.

These processes will be

  • Inherently "green", since the unwanted enantiomer is transformed into the desired enantiomer;
  • Enabled by mechanochemistry, which eliminates the need for solvent, making them "greener" than solution-based methods.
  • The "greenest" possible, thanks to their efficiency (very fast timescale and low energy consumption).

Catherine Michaux, Stéphane Vincent and Guillaume Berionni were awarded equipment financing (EQP).

This funding will enable the acquisition of high-throughput isothermal titration calorimetry (ITC) equipment, unique in the Wallonia-Brussels Federation. This is a high-resolution, non-destructive method enabling complete characterization of the chemical details of an interaction in solution.

His acquisition will enable UNamur chemists, but also their collaborators, to analyze any bond, in a vast field of application, extending from biochemistry to supramolecular chemistry.

FRIA doctoral scholarship - Noah Deveaux (PI - Benoît Champagne)

"ONL molecular switches "in all their states": from solutions to functionalized surfaces and solids."

This PhD thesis within the Theoretical Chemistry Laboratory (Department of Chemistry) and the Multiscale Modeling through High-Performance Computing (HPC-MM) Cluster of the NISM Institute aims to develop innovative multiscale computational methodologies to study and optimize multistate and multifunctional molecular switches, key components of logic devices and new generations of data storage technologies.

In addition to variations in linear optical responses, it is advantageous to consider changes in nonlinear optical responses (NLOs), which enable high-resolution data readout while avoiding their destruction. The main objective is to predict and interpret the ONL responses of these molecular switches in different matter environments, namely in solution, grafted onto surfaces and in the solid state.

In addition, particular attention will be paid to modeling defects and orientational disorder within materials to better represent real-world conditions. These predictive methods will be validated experimentally through close collaborations with synthesis and characterization teams.

FNRS, la liberté de chercher

Chaque année, le F.R.S.-FNRS lance des appels pour financer la recherche fondamentale.  Il a mis en place une gamme d'outils permettant d’offrir à des chercheurs, porteurs d’un projet d’excellence, du personnel scientifique et technique, de l’équipement et des moyens de fonctionnement.

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The NISM Institute

Research at NISM revolves around a variety of research topics in organic chemistry, physical chemistry, (nano)-materials chemistry, surface science, optics and photonics, solid-state physics, both from a theoretical and experimental point of view.

Researchers' expertise is recognized in the synthesis and functionalization of molecular systems and innovative materials, from 0 to 3 dimensions.